4-Aminopyridine-2,3-dicarboxylic acid

A new metabolite, 4-aminopyridine-2,3-dicarboxylic acid, was recently isolated from C. acromelalga in a yield of 0.000056% based on the weight of frozen fruiting bodies (41)5). A lethal effect of this compound on mice has not been observed however, bioactivity is still expected because of the similarity of its structure to the physiologicaUy active pyridine-2,3-dicarboxylic acid. The structure of this compound was deduced from H-NMR, C-NMR, and mass spectra, and the position of the substituents was assumed from comparison with clitidine, which contains a 4-aminopyridine-3-carboxylic acid moiety. The structural proposal was confirmed by synthesis from 2,3-dimethyl-4-nitropyridine 1-oxide (Scheme 91) when this compound was subjected to successive reduction and oxidation it yielded a product identical to the one occurring naturally. 

Hirayama, F., Konno, K., Shirahama, H., Matsumoto, T., 4-Aminopyridine-2,3-dicarboxylic acid from Clitocybe acromelalga. Phytochemistry, 28,1133-1135... 

Examples of co-crystals containing chains, ribbons, and other infinite 1-D motifs, Scheme 2.5.15, include bipyridine dihydroxybenzene [99], melaminexyanuric acid [100], bipyridine (fluorinated)dibromobenzene [101], bypyridine (diiodoben-zene, tetraiodoethylene or diiodine) [102], 2-aminopyridine dicarboxylic acids... 

Fig. 10 X-ray crystal structure of 2(biphenyl-3,3 -dicarboxylic acid) 2(isophthalyl bis(aminopyridine).

Following the work of Whitesides, Hamilton reported a cyclic assembly based on a biphenyl-3,3 -dicarboxylic acid and an isophthalpyl bis(aminopyridine) (Fig. 10).25 The four-component assembly, of composition 2(acid) 2(bipyridine), was held together by eight hydrogen bonds. The components adopted a figure-of-eight structure in the solid state, wherein the diacids and bipyridines participated in face-to-face 7i-7i forces. 

Aminopyridines and pyrimidines preferentially hydrogen bond to carboxylic acids. Tellado et al. showed that a unit containing two aminopyridine groups separated by a rigid spacer is a receptor for dicarboxylic acids with a correspondence between the length of the spacer and that of the carboxylic acid [70]. This is illustrated in Figure 7. 

Examples of cocrystals containing chains, ribbons, and other infinite ID motifs (Scheme 8) include bipyridine dihydroxybenzene, melamine cyanuric acid, bipyridine (fluorinated)dibromobenzene, 2-aminopyridine dicar-boxylic acids, triaminopyrimidine barbituric acid, 2-aminopyrimidine dicarboxylic acid, " 1,2,3-trihydroxy-benzeneihexamethylenetetramine, diols diamines, bis-benzimidazole dicarboxylic acids, and 2-amino-5-nitro-pyrimidine 2-amino-3-nitropyridine." ... 

Reactions of 2-aminopyridines and diethyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-l,3-dicarboxylate (309) in acetic acid for 4 h gave either ethyl 1,2-dihydro-l 1-oxo-l l//-pyrido[2,l -6]quinazoIine-2-carboxylates (310) or their isomeric ethyl 7,8-dihydro-6-oxo-6//-pyrido[l,2-a]quinazoline-8-carboxylates (311) (92PHA336). 

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